Cancer cells must interact with endothelium prior to the extravasation step of the metastatic process. We have developed a syngeneic rat metastasis model that utilizes oncogene transformed, LacZ transfected tumor cells, which can be located histochemically as single cells. Metastatic, adhesive and proteolytic profiles of v-raf (R3611) and v- raf/v-myc (RJ2-14) transformed rat liver epithelial (RLE) cells were determined. The RJ2-14 cells were spontaneously metastatic in syngeneic Fischer 344 rats and nude mice. They adhered poorly to all substrates, except laminin. Adhesion to a confluent monolayer of endothelial cells was not affected by prior exposure of the endothelial cells to TGF-beta, IL-1 beta, or TNF-alpha. However, 10 min preincubation of the endothelial cells with thrombin (1 u/ml) stimulated adhesion of the metastatic R3611 and RJ2-14 cells, but had no effect on the adhesive capacity of the normal parent RLE cells. The increase in tumor cell adhesion was inhibited by EDTA, heparin and dextran sulfate, but not by staurosporin. The data suggest that a granule membrane protein (GMP-140), a receptor for neutrophils and monocytes on activated endothelium, is responsible for the thrombin-mediated increase of tumor cells to endothelium. Six metastatic and nonmetastatic v-raf transformed R3611 single cell clones had a similar profile of metalloproteinase and plasminogen activator expression in vitro. However, 185 kDa nonmetalloproteinase was detected in tumor homogenates derived from the metastatic, but not the nonmetastatic clones. Ongoing studies focus on microvascular endothelial cell interactions with meta-static and nonmetastatic tumor cells in the rat model to further understand the pathogenesis of tumor cell arrest and extravasation.